BackgroundBAY 81-8973 is a new full-length human recombinant factor VIII product manufactured with technologies to improve consistency in glycosylation and expression to optimize clinical performance.ObjectivesTo demonstrate superiority of prophylaxis vs. on-demand therapy with BAY 81-8973 in patients with severe hemophilia A.Patients/MethodsIn this multinational, randomized, open-label crossover study (LEOPOLD II; ClinicalTrials.gov identifier: NCT01233258), males aged 12–65 years with severe hemophilia A were randomized to twice-weekly prophylaxis (20–30 IU kg−1), 3-times-weekly prophylaxis (30–40 IU kg−1), or on-demand treatment with BAY 81-8973. Potency labeling for BAY 81-8973 was based on the chromogenic substrate assay or adjusted to the one-stage assay. Primary efficacy endpoint was annualized number of all bleeds (ABR). Adverse events (AEs) and immunogenicity were also assessed.ResultsEighty patients (on demand, n = 21; twice-weekly prophylaxis, n = 28; 3-times-weekly prophylaxis, n = 31) were treated and analyzed. Mean ± SD ABR was significantly lower with prophylaxis (twice-weekly, 5.7 ± 7.2; 3-times-weekly, 4.3 ± 6.5; combined, 4.9 ± 6.8) vs. on-demand treatment (57.7 ± 24.6; P < 0.0001, anova). Median ABR was reduced by 97% with prophylaxis (twice-weekly, 4.0; 3-times-weekly, 2.0; combined, 2.0) vs. on-demand treatment (60.0). Median ABR was higher with twice-weekly vs. 3-times-weekly prophylaxis during the first 6-month treatment period (4.1 vs. 2.0) but was comparable in the second 6-month period (1.1 vs. 2.0). Few patients reported treatment-related AEs (4%); no treatment-related serious AEs or inhibitors were reported.ConclusionsTwice-weekly or 3-times-weekly prophylaxis with BAY 81-8973 reduced median ABR by 97% compared with on-demand therapy, confirming the superiority of prophylaxis. Treatment with BAY 81-8973 was well tolerated.

The FUT2 genes encoding for the phenotypes Le(a+b+) and Le(a+b-) are the same. The function and character of the mutant enzyme may play an important role in the phenotype. The methods used in this study are clinically applicable in population studies of the FUT2 gene polymorphism to explore relationships among different ethnic groups and correlations between phenotype and genotype.

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Aim-To compare the eYcacy and safety of an indomethacin treatment strategy based on serial echocardiographic measurement of patent ductus arteriosus (PDA) flow pattern with a standard protocol. Methods-Neonates weighing less than 1500 g at birth, who required respiratory support, and who had developed symptomatic PDA, were studied. PDA was confirmed in all infants using colour Doppler echocardiography, and serial observations of the ductal flow pattern were made. Infants randomly assigned to receive conventional indomethacin treatment (protocol group) were given an initial dose of 0.2 mg/kg, followed by 0.1 or 0.2 mg/kg, depending on age, 12 hourly for two further doses, and were eligible for a second course. Those randomly assigned to the ductal flow pattern assessment (ECHO group) received further doses of indomethacin after 24 hours, only if their flow pattern was "pulsatile" or "growing." Results-There was no significant diVerence in the primary outcome measures between the two groups. The closure rate was 89.1% and 87.2%, respectively, in the protocol and ECHO groups. The mean (SD) doses of indomethacin were significantly higher in the protocol group: 3.2 (1.4) doses compared with 1.6 (0.9) doses. There was a significantly higher incidence of hypoglycaemia, impaired urine output, and gastrointestinal bleeding in the protocol group. Conclusions-An indomethacin treatment strategy for PDA based on measurement of the ductal flow pattern is associated with a reduction in the total doses of indomethacin administered, and a reduced rate of complications, compared with a conventional protocol. There is no diVerence in closure rate.

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ObjectiveTo describe the epidemiological characteristics of infantile hypertrophic pyloric stenosis (IHPS) in ethnic Chinese children.Materials and MethodsWe reviewed the National Health Insurance claims database and analyzed data from children less than one year of age who had been diagnosed with IHPS (ICD-9-CM 750.5) and had undergone pyloromyotomy (ICD-9-CM 43.3). We analyzed the incidence, gender, age at diagnosis, length of hospital stay, seasonal variation and cost of IHPS from data collected between January 1997 and December 2007.ResultsA total of 1,077 infants met inclusion criteria, including 889 boys and 188 girls. The annual incidence of IHPS ranged from 0.30 to 0.47 per 1,000 live births with a mean incidence of 0.39 per 1,000 live births. Between 2002 and 2007, the incidence showed a declining trend (P = 0.025) with coincidentally increasing trends for both exclusive breastfeeding (P = 0.014) and breastfeeding plus bottle feeding (P = 0.004). The male-to-female rate ratio was dynamic and increased from 3.03 during the first two weeks of life to 8.94 during the 8th through 10thweeks of life. The overall male-to-female rate ratio was 4.30. The mean age at diagnosis was 43.1±2.4 days. After analyzing the months of birth and hospital admission, no seasonal variation associated with IHPS was detected. The mean length of hospital stay was 8.28±7.10 days.ConclusionsThe incidence of IHPS in Taiwan, a country with a majority ethnic Chinese population, was lower than observed incidences in Caucasian populations living in Western countries. Breastfeeding campaigns and low maternal smoking rates may contribute to the lower incidence of IHPS in Taiwan. However, additional studies with longer follow-up periods are needed.

We conducted a prospective 3-yr clinical study comparing deferiprone (L1) with desferrioxamine (DFX). The therapeutic efficacy and potential side-effects on cardiac and/or hepatic systems of thalassemia patients were assessed by left ventricular ejection fraction, T2-weighted magnetic resonance imaging, and biochemical parameters. In both groups, levels of serum ferritin decreased significantly, and the hepatic function improved notably. Besides decrement of iron, no marked pathohistological changes were observed in the liver biopsies. These results indicated that for patients who failed to respond to DFX treatment, the use of L1 to remove excess iron deposition is recommended.

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